Abstract
Recent advances in high throughput genotyping technologies will allow large-scale association studies to disentangle the genetic basis of human common diseases. Currently, a large-scale genotyping effort is being carried out by the HapMap project and the outcome of this project is expected to help researchers in their efforts to understand how genetic variation influences susceptibility to disease. However, there is some controversy on whether this huge public effort will be of value for those populations not studied in the HapMap project. Here, we present simulation results based on the empirical distribution of linkage disequilibrium (LD) on a large chromosomal region (10 Mb) on human chromosome 201,2 for two European and two Asian populations. These results show that statistical power to detect associations does not depend on the population were SNP tagging was performed.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Ke X, Durrant C, Morris AP et al: Efficiency and consistency of haplotype tagging of dense SNP maps in multiple samples. Hum Mol Genet 2004; 13: 2557–2565.
Ke X, Hunt S, Tapper W et al: The impact of SNP density on fine-scale patterns of linkage disequilibrium. Hum Mol Genet 2004; 13: 577–588.
Hirschhorn JN, Daly MJ : Genome-wide association studies for common diseases and complex traits. Nat Rev Genet 2005; 6: 95–108.
Nielsen R, Hubisz MJ, Clark AG : Reconstituting the frequency spectrum of ascertained single-nucleotide polymorphism data. Genetics 2004; 168: 2373–2382.
Terwilliger JD, Haghighi F, Hiekkalinna TS, Goring HHH : A bias-ed assessment of the use of SNPs in human complex traits. Curr Opin Genet Dev 2002; 12: 726–734.
Meng Z, Zaykin DV, Xu CF, Wagner M, Ehm MG : Selection of genetic markers for association analyses, using linkage disequilibrium and haplotypes. Am J Hum Genet 2003; 73: 115–130.
Weir BS : Genetic Data Analysis II. Sunderland, MA: Sinauer Associates, 1996.
Carlson CS, Eberle MA, Rieder MJ, Yi Q, Kruglyak L, Nickerson DA : Selecting a maximally informative set of single-nucleotide polymorphisms for association analysis using linkage disequilibrium. Am J Hum Genet 2004; 74: 106–120.
Hill WG, Robertson A : Linkage disequilibrium in finite populations. Theo Appl Genet 1968; 38: 226–231.
Ahmadi KR, Weale ME, Xue ZY et al: A single-nucleotide polymorphism tagging set for human drug metabolism and transport. Nat Genet 2005; 37: 84–89.
Mueller JC, Lohmussaar E, Magi R et al: Linkage disequilibrium patterns and tagSNP transferability among European populations. Am J Hum Genet 2005; 76: 387–398.
Evans DM, Cardon LR : A comparison of linkage disequilibrium patterns and estimated population recombination rates across multiple populations. Am J Hum Genet 2005; 76: 681–687.
Acknowledgements
We thank Peter Visscher and Naomi Wray for helpful comments on an early version of the manuscript and Ian White and Andrew Carothers for helpful discussions on PCA. The relevant work on genetic susceptibility to colorectal cancer ongoing in these laboratories is funded by a Cancer Research UK Programme Grant (C348/A3758) and by grants from the Scottish Executive Chief Scientist Office (K/OPR/2/2/D333 and CZB/4/94) and by the Medical Research Council (G0000657-53203). AT is funded by Grant C348/A3758.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tenesa, A., Dunlop, M. Validity of tagging SNPs across populations for association studies. Eur J Hum Genet 14, 357–363 (2006). https://doi.org/10.1038/sj.ejhg.5201554
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.ejhg.5201554
Keywords
This article is cited by
-
Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21
Nature Genetics (2008)
-
A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition
BMC Genetics (2007)
-
Evaluation of the SNP tagging approach in an independent population sample—array-based SNP discovery in Sami
Human Genetics (2007)
-
Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy
Human Genetics (2007)
-
Efficient selection of tagging single-nucleotide polymorphisms in multiple populations
Human Genetics (2006)
